The endothelial protein C receptor (EPCR) facilitates protein C activation and plays a protective role in the response toEscherichia coli–mediated sepsis in primates. Previously, a soluble form of EPCR (sEPCR) in human plasma was characterized, and several studies indicated that generation of sEPCR is regulated by inflammatory mediators, including thrombin-mediated up-regulation of surface metalloproteolytic activity in vitro. This study addressed the question of whether plasma sEPCR levels reflect changes in thrombin generation in patients undergoing anticoagulant treatment. The sEPCR levels in patients treated with coumarin-type oral anticoagulants were significantly lower than those in healthy asymptomatic adult volunteers (105.3 ± 70.8 ng/mL [n = 55] versus 165.8 ± 115.8 ng/mL [n = 200]; P